This disclosure concerns the field of immunology. More particularly this disclosure relates to compositions and methods for eliciting an immune response that reduces infection and/or symptoms of infection by the leading causes of lower respiratory tract infection.
Human Respiratory Syncytial Virus (RSV), human Metapnumovirus (hMPV), and Parainfluenza viruses (PIV1-4) are the most common causes of lower respiratory tract infections (LRI) in infants less than one year of age. The spectrum of disease caused by these viruses includes a wide array of respiratory symptoms from rhinitis and otitis to pneumonia and bronchiolitis, the latter two diseases being associated with considerable morbidity and mortality.
Respiratory syncytial virus (RSV) is a pathogenic virus of the family Paramyxoviridae, subfamily Pneumovirinae, genus Pneumovirus. The genome of RSV is a negative-sense RNA molecule, which encodes 11 proteins. Tight association of the RNA genome with the viral N protein forms a nucleocapsid wrapped inside the viral envelope. Two groups of human RSV strains have been described, the A and B groups, based on differences in the antigenicity of the G glycoprotein.
Human metapneumovirus (hMPV), like human respiratory syncytial virus (RSV), is classified in the Pneumovirinae subfamily of the Paramyxoviridae family. However, hMPV is most closely genetically related to avian metapneumovirus (formerly called turkey rhinotracheitis virus). These two viruses are classified in the genus Metapneumovirus, with hMPV the first in this genus to cause disease in humans. hMPV was first described in 2001 by researchers in the Netherlands, and has since been identified in countries on all continents except Antarctica. hMPV is a single negative-stranded RNA-enveloped virus. Two major groups (A and B) and 4 subgroups of hMPV have been identified to date.
Human parainfluenza viruses are a group of paramyxoviruses that rank second only to respiratory syncytial virus (RSV) as a cause of lower respiratory tract disease in young children. Human parainfluenza viruses are classified in the Paramyxovirinae subfamily, Respirovirus genus. Like RSV, human parainfluenza viruses (HPIVs) can cause repeated infections throughout life. These infections are usually manifested by an upper respiratory tract illness (such as a cold or sore throat). HPIVs can also cause serious lower respiratory tract disease with repeat infection (including pneumonia, bronchitis, and bronchiolitis), especially among the elderly, and among patients with compromised immune systems. Each of the four HPIVs (serotypes 1-4) has different clinical and epidemiologic features. The most distinctive clinical feature of HPIV-1 and HPIV-2 is croup (laryngotracheobronchitis). HPIV-3 is most often associated with severe lower respiratory disease, including bronchiolitis and pneumonia. HPIV-4 is infrequently associated with severe disease.
Various approaches have been attempted in efforts to produce a safe and effective vaccines against these respiratory viruses that produces durable and protective immune responses in healthy and at risk populations. However, none of the candidates evaluated to date have been proven safe and effective as a vaccine for the purpose of preventing infection and/or reducing or preventing disease, including lower respiratory infections (LRIs), caused by these viruses.